title: Plasma choline, nicotine exposure, and risk of low bone mineral density and hip fracture: the Hordaland health study.
abstract: Choline, obtained from diet and formed by biosynthesis, is the immediate precursor of betaine. Animal studies suggest an impact of choline on bone metabolism. We examined the associations of plasma choline and betaine with bone mineral density (BMD), the risk of hip fractures, and possible effect-modification by nicotine exposure. The Hordaland Health Study (1998 to 2000) included 7074 women and men (ages 46 to 49 or 71 to 74 years). In 5315, BMD was measured. The oldest (n = 3311) were followed for hip fractures through 2009. Risk associations were studied by logistic and Cox regression by comparing the lowest and middle tertiles with the highest, as well as trends across tertiles of plasma choline and betaine. In analyses adjusted for sex and age, participants in the lowest (odds ratio [OR] = 2.00, 95% confidence interval [CI] 1.69-2.37) and middle (OR = 1.39, CI 1.17-1.66) tertiles of plasma choline had an increased risk of low BMD (lowest quintile) (p trend < 0.001). Separate analyses for sex and age groups revealed the strongest relations in elderly women (lowest tertile: OR = 2.84, CI 1.95-4.14; middle tertile: OR = 1.80, CI 1.22-2.67, p trend < 0.001), and highest OR among those in the lowest tertile who were exposed to nicotine (OR = 4.56, CI 1.87-11.11). Low plasma choline was also associated with an increased risk of hip fracture in elderly women and men (lowest tertile: hazard ratio [HR] = 1.45, CI 1.08-1.94; middle tertile: HR = 1.13, CI 0.83-1.54, p trend = 0.012). In elderly women, the HR for hip fracture was 1.90 (CI 1.32-2.73) and 1.36 (CI 0.92-1.99) (p trend < 0.001) for lowest and middle tertiles of choline, and the highest HR was found among women in the lowest tertile exposed to nicotine (HR = 2.68, CI 1.16-6.19). Plasma betaine was not related to BMD or hip fracture. Low plasma choline was associated with low BMD in both sexes and increased the risk of hip fracture in elderly women. These results should motivate further studies on choline, nicotine exposure, and bone metabolism.
authors.affiliation: Department of Rheumatology, Haukeland University Hospital, Bergen, Norway; Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
authors.forename: Jannike
authors.initials: J
authors.lastname: Øyen
authors.forename: Ottar Kjell
authors.initials: OK
authors.lastname: Nygård
authors.forename: Clara Gram
authors.initials: CG
authors.lastname: Gjesdal
authors.forename: Per Magne
authors.initials: PM
authors.lastname: Ueland
authors.forename: Ellen Margrete
authors.initials: EM
authors.lastname: Apalset
authors.forename: Hall
authors.initials: H
authors.lastname: Schartum-Hansen
authors.forename: Stein Emil
authors.initials: SE
authors.lastname: Vollset
authors.forename: Klaus
authors.initials: K
authors.lastname: Meyer
authors.forename: Grethe S
authors.initials: GS
authors.lastname: Tell
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D001622:Betaine / Q000097:blood; D015519:Bone Density; D002794:Choline / Q000097:blood*; D005260:Female; D006620:Hip Fractures / Q000453:epidemiology / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000009:adverse effects* / Q000494:pharmacology; D009664:Norway / Q000453:epidemiology; D016017:Odds Ratio; D012307:Risk Factors
chemical_list: D001622:Betaine; D009538:Nicotine; D002794:Choline
keywords: BONE MINERAL DENSITY; HIP FRACTURE; NICOTINE EXPOSURE; PLASMA BETAINE; PLASMA CHOLINE; PLASMA COTININE